Objective. Negative pressure therapy (NPT) offers the potential to reduce infection in obese patients. The goal of this study was to explore the association between NPT use and infection after cesarean delivery among obese women. Methods: We initiated a hospital protocol wherein women with a body mass index (BMI) of 40 kg/m2 or greater who delivered after January 1, 2011 were to receive NPT following cesarean section. A retrospective comparison of surgical site infection (SSI) in women receiving the intervention to a similar group with a BMI of 40 kg/m2 or greater, a historical control group of women who delivered before January 1, 2011. Incidence of SSI was compared between time periods using logistic regression models. Results. A total of 233 patients in the preintervention (control) group and 234 patients in the intervention group were included in the analysis. In the control group, 23 (9.9%) developed SSI, compared with 13 (5.6%) in the intervention group. After adjustment for potential confounding factors, women in the postintervention period experienced a statistically significant reduction in SSI rates (adjusted odds ratio =0.45, 95% CI = 0.22-0.95); P = .04). Conclusion. Implementation of a hospital protocol of NPT following cesarean delivery in obese women resulted in reduced incidence of postoperative SSI. This study suggests that using NPT after cesarean delivery in women with a BMI ≥40 kg/m2 is an efficacious method to reduce incidence of postoperative wound infections.